superantigen microbiology presentation
TRANSCRIPT
-
8/12/2019 Superantigen Microbiology Presentation
1/18
Presented by:
Shymaa Yousry Hassan
[602]
-
8/12/2019 Superantigen Microbiology Presentation
2/18
Structure Superantigens are medium sized 22-29 kDa
globular compact proteins.
Crystal structures: ellipsoidal proteins withcharacteristic two domain protein folding.
Have sites for binding MHC II and TCRs.
-
8/12/2019 Superantigen Microbiology Presentation
3/18
Structure Two-domain folding pattern and architecture
(N and C terminal domains and helix in the center of the molecule)
NH2-terminal barrel globular domain known as
the oligosaccharide/oligonucleotide fold
Long -helix that diagonally spans the center ofthe molecule
COOH terminal globular domain
-
8/12/2019 Superantigen Microbiology Presentation
4/18
Structure The Nterminal domain:
Hydrophobic residues in solvent exposed regions
Determines the lethalityof the toxin.
The Cterminal domain: Four stranded sheet capped by the central helix
Determines the superantigenicityof the toxin.
-
8/12/2019 Superantigen Microbiology Presentation
5/18
Structure Each superantigen possesses slightly different
binding modes when it interacts with MHC classII molecules or the T-cell receptor.
-
8/12/2019 Superantigen Microbiology Presentation
6/18
Special characters Presence of disulphide loop formed by the
cystinyl residues (except in TSST I)in the Nterminaldomain [emetic properties of the enterotoxins].
TSST-I:no extrastructural characters=> cleaved bypepsin.
SE and SPE:extrastructural characters like:
Lengthy amino terminal [resist the peptidedigestion in the stomach => Staphylococcal foodpoisoning].
Emetic property: cystinyl residues.
-
8/12/2019 Superantigen Microbiology Presentation
7/18
Normally..
-
8/12/2019 Superantigen Microbiology Presentation
8/18
However,.. The unique feature of superantigen is that it
bypasses the antigen processing mechanismand specifically binds to TCR v segment andforms a trimolecular complex along with majorhistocompatibility complex class II.
-
8/12/2019 Superantigen Microbiology Presentation
9/18
-
8/12/2019 Superantigen Microbiology Presentation
10/18
Mechanism of action. Superantigens bind to MHC class II molecules of
antigen presenting cells and V region of T-cellreceptor in a non-antigen-specific manner.
Stimulation of large number of T cells resulting incell activation, differentiation, proliferation, andproduction of cytokinesinvolved in variousinflammatory processes.
-
8/12/2019 Superantigen Microbiology Presentation
11/18
Activation
-
8/12/2019 Superantigen Microbiology Presentation
12/18
Effects of superantigenstimulation IL - I and TNF- bring about the vascular
endothelial injury [toxic shock syndrome].
of IL- 6, GM-CSF and E-selectin elicitproinflammatory and prothrombic responses[Kawasaki syndrome].
-
8/12/2019 Superantigen Microbiology Presentation
13/18
-
8/12/2019 Superantigen Microbiology Presentation
14/18
Direct Effects Thcells: IL-1, IL-2, IL-6, TNF-, Macrophage
Inflammatory protein, Macrophagechemoattractant protein.
Fever, rash, multi organ failure, coma & death.
IL-10 [non responsive memory cells]: Deletion ofactivated T.
INF : prolonged SAg exposure, induces autoimmunity[Kawasaki disease]
MHC cross-linking: up-regulates apoptosis.
-
8/12/2019 Superantigen Microbiology Presentation
15/18
Indirect Effects Mitogenic activity.
Monocytic cell activation & release of large
amounts of TNF-: tissue necrosis Induce gastrointestinal toxicity and cause
emesis: by SAg produced by bacteria causingfood poisoning [SE and SPE].
-
8/12/2019 Superantigen Microbiology Presentation
16/18
Interaction of T cell receptor (TCR) and MHC loaded with antigenicpeptide during the normal T cell activation (A) and duringsuperantigenic activation by staphylococcal enterotoxins (B). Thelatter can be inhibited by polyclonal antibodies such as anti-SEBhyperimmune serum as shown in (C).
-
8/12/2019 Superantigen Microbiology Presentation
17/18
Indirect Effects Monocytic cell activation and release of large
amounts of TNF-leading to tissue necrosis.
Emesis: by SAg produced by bacteria causingfood poisoning.
Induction of gastrointestinal toxicity and emesis.
-
8/12/2019 Superantigen Microbiology Presentation
18/18
Consequences Shock: massive release of cytokines.
Immunosupression: uncoordinated activation of
immune system. Autoimmunity: bypass of auto reactive T & B cells